Here Is a Human Being Read online

  Despite George’s “put-it-all-on-the-Web” openness, at one point he expressed misgivings to me that both he and Halamka had outed themselves as subjects before recruiting the rest of the first ten PGPers. I didn’t get it—wasn’t this the whole point of the PGP exercise? Shouldn’t all the subjects be screaming their identities from the rooftops? “I just think it’s a team effort and we need to have a little bit of team consideration,” he said. “Even if it’s something we all plan to do eventually, maybe we all want to do it together, maybe we want to have a press release, maybe we want to make sure that the look and feel of the database are up to snuff before we do it. There are timing issues. There are issues about whether we portray it in a positive light but with enough discussion of the negative aspects. I think that requires some nuance that the really gung-ho people will be too impatient to do. I think this is a work in progress, a successive approximation.”23

  For months I periodically emailed or called George to ask about the status of the PGP recruits: Had they all been picked, had the IRB given them the okay, had they signed the consent form, had they had their blood drawn? The process seemed to be moving at a crawl. I eventually gave up on becoming a subject. George had received hundreds of responses to his call for volunteers. Everyone wanted his or her genome sequenced for free. I imagined that George figured I would write about the project anyway, so why should he even bother to recruit me and risk the possibility that I might write something unflattering? As a science editor I had grown used to dealing with finicky and occasionally prickly scientists fretting over whether writers were capable of getting their work right (the presumption was usually no, they weren’t) and whether my portrayals would reflect well on them. I resigned myself to the idea that my role would be to go on masquerading as a journalist. Like Jon Stewart, only not as funny.

  One night a message appeared in my inbox. “The Harvard Medical School Institutional Review Board has just approved you as a participant in the study, so if you are still interested …”24 Ha! George really takes this opt-out thing seriously, I thought, though I suspected he was smiling as he typed it.

  Ann had just turned out the light and was drifting off to sleep. “I’m in,” I announced. “Congratulations, that’s great,” she said. She was quiet for a moment.

  “Or maybe it’s not. I guess we’ll find out.”

  When I told friends and colleagues I was officially a PGP subject, after the “Why do this?” question usually came the “Why you?” one. Or, as one said, “What makes you so special, Genome Boy?” Nothing. Nothing makes me special: that’s the whole idea. (That exchange, however, did prompt me to start a blog called genomeboy.com.)

  But in the early days a fair number of scientists and bioethicists perceived personal genomics as special to a fault: in their eyes it was a purely self-indulgent exercise. One bioethicist I know said she thought the sequencing of Watson, Venter, Church, et al. would “help identify the megalomania gene.” A May 2007 article in Nature was headlined “Celebrity Genomes Alarm Scientists.” In it, fly geneticist extraordinaire and onetime Venter nemesis Michael Ashburner called sequencing “famous or very rich people … bloody tacky.” The Genetics & Public Policy Center’s Kathy Hudson said that if this is what came out of the Human Genome Project, it would be “sort of a sad statement.” Then–National Human Genome Research Institute director Francis Collins took a veiled (but probably justified) shot at Watson for not consulting his family members before getting sequenced. At the head of the article were smiley pictures of Venter, Watson, and George, the Unholy Trinity of Personal Genomics made to do a perp walk across the pages of science’s most hallowed publication.25

  As a PGP subject I could hardly claim to be objective. But to me this smacked of a double standard. On the one hand, the noble souls at the NIH wanted to protect poor, naïve research subjects and their genomic data; on the other, they seemed to have abiding contempt for the early adopters. If a potential research subject was poor, uneducated, or a minority, then the knee-jerk response was that that person was ripe for exploitation. I get that—the history of genetics is littered with examples of bad behavior toward folks who could not defend themselves, from American eugenics to the Nuremberg laws to Nazi medical experiments to the Tuskegee “studies” of untreated syphilis in African American males that dragged on for forty cruel, inhuman years.26 But did these outrages necessarily imply the converse to be true? If someone white, educated, and relatively advantaged chose to participate in a cutting-edge experiment, was it fair to presume he or she would reap some enviable benefit or was doing it only for elitist navel-gazing purposes?

  I attended the Biology of Genomes meeting at Cold Spring Harbor Laboratory (CSHL) in May 2007. Not so long ago this gathering was called the “Genome Mapping & Sequencing Meeting"; now, in the postgenome era, it was much more about actual biology, that is, how cells work, than about just amassing DNA sequence. The 2007 edition featured lively presentations on Neanderthals, biofuels, and genes that make dogs run faster. There were plenty of famous geneticists around, but the gathering still felt very bottom-up: students and postdocs outnumbered their bosses; they razzed them from the podium and drank with them in the evenings. For me it was nostalgia-inducing. I recalled my days as a real scientist in training, staying up late making posters or PowerPoint slides and then sprinting to catch a train or plane to some exotic locale, making my presentation, and heading to the bar for a long night of revelry interspersed with grad-student talk about genes, postdocs, and life.

  When I arrived it was a gorgeous day in early May and everything was already lush in the aftermath of rain and warm temperatures. I saw Chad Nusbaum, sequencing guru from the MIT-Harvard Broad Institute whom I’d met at a few months earlier at the genome technology meeting in Florida, cavorting on the lawn behind the dining hall in shorts, a T-shirt, and bare feet. Chad would often jog the eight miles to work in the Boston snow and ice. Seeing him now I was jealous: in my long-sleeve shirt and sport coat I not only looked every bit the outsider, I was practically panting from the heat as I waded through the lunch line.

  The lab—a sprawling campus, actually, that was the unofficial home of the early-twentieth-century eugenics movement27—is nestled on a pristine inlet on Long Island Sound. Manhattan is thirty-five miles west but might as well be on the other side of the world. The harbor was dotted with boats and birds; geese squawked overhead. The lucky/well-connected folks got to stay on campus in dorms or the rustic clapboard houses. The rest of us were shuttled to and from the Holiday Inn in a neighboring town.

  I was here to try to see Jim Watson, former president of CSHL and, before some unfortunate remarks about race he would make a few months later,28 president emeritus of the lab. Watson landed here in 1968, the year he published his shockingly impolite memoir The Double Helix,29 and fifteen years after he and Francis Crick discovered the double helix itself, for which they won the Nobel Prize in 1962.30 I wanted to ask Watson about his decision to get his genome sequenced, how he felt about it, why he’d decided not to learn about his status for APOE (the most important common Alzheimer’s susceptibility gene31) and what if anything his precedent might mean for the PGP.

  Someone at CSHL had made inquiries on my behalf. He reported that “Jim’s people” said he was not giving interviews until the end of the month, when there was to be a big event at Baylor University in Houston honoring the completion of his genome. My friend said that maybe I could meet him casually and chat with him but warned me not to push. Watson had long been considered a loose cannon, a trait both he and his handlers recognized (some less recent things he’s said: “The best home for a feminist is another person’s lab,”32 organismal biologists are just “stamp collectors,” “anyone who would hire an ecologist is out of his mind,”33 “I’ve never read the Bible; I’m not sure I’ve missed much,”34 etc.). Friends told me that the lab had tried to rein him in over the years but without much success. “You never know what the hell he’s going to say,” admitted a oneti
me instructor at a CSHL summer course whose students Watson used to address. She had no idea how prescient she was.

  As the meeting went on, he was not around much, save for an outdoor book-signing event for the newest edition of the breezy (no, really) textbook Recombinant DNA.35 I joined the crowd on the veranda just off the bar/café and grudgingly plunked down my credit card (eighty-three dollars … for a paperback!) in hopes of gaining a little access. I watched him squinting through his glasses and breathing loudly through his nose, his expression inscrutable. He was engrossed in the act of signing his name, which he did ever so slowly and meticulously in small print, occasionally lifting his head to chat with his coauthors. He barely acknowledged the queue of giddy but polite young scientists. I opened my mouth to say something, only to wimp out and shrink away in authentic fake-journalist fashion. I had been reading about this guy in textbooks for most of my adult life, gazing at his picture, listening to outrageous stories about him. Now, after twenty years, here was my chance and I flinched.

  I tried to convince myself that I could craft a composite Watson by talking to the other folks involved in Project Jim. Michael Egholm was vice president of research and development for 454 Life Sciences (bought by Roche in 2007), the company that was first to market with its next-generation DNA sequencer. Project Jim was a million-dollar effort36 (or maybe $2 million, depending upon whom you asked37) initiated by 454 together with Baylor sequencing czar Richard Gibbs, presumably as a way for the company to garner publicity for its new machines.38 I approached Egholm, an affable if cocky Dane with slicked-back hair, a pink tint to his face, and wire-rimmed glasses. He promised that at the Houston event Watson would be given his genome sequence and that at about the same time there would be a paper published (“hopefully in a good journal”) and then, in a symbolic flourish, Watson himself would deposit his sequence into GenBank, the public home of all known freely available DNA sequence information.* The question of what part of his genomic information would be redacted beyond APOE was an open one. “We have a list of bad genes,” Egholm told me. “We’re simply going to walk him through that list and ask him what he wants. The real discussion is, what do his relatives say? The concern is that a year or two from now we’re going to discover that if one has this or that allele, one will drop dead at a certain age. Jim doesn’t really care about that—he likes to rub that in, you know, that even at his advanced age he doesn’t have any maladies. The real concern is about his descendants.” Watson had two grown sons, one of whom was schizophrenic.

  In practical terms, Egholm said that for next-generation sequencing, data analysis remained the biggest challenge, especially for an entire human genome sequenced six or seven times over. “Twenty billion bases is still twenty billion bases. There’s no way around it.”39 (This was in 2007. Six- or seven-fold sequencing coverage [about 20 billion bases] of a human genome would soon be considered laughable. The first sequenced Asian and African genomes, for example, were sequenced at more than 30x coverage, or about 100 billion bases, which became something of an informal standard.)

  One difference between Project Jim and the PGP was that the former was not originally conceived of as research at all. Rather, it was an agreement between a company, 454, and a private individual, Watson. When in early 2007 Baylor medico-legal scholar Amy McGuire was brought in to address the ethical aspects of Project Jim, the first thing she did was push to restructure it as a research protocol. This meant drafting a more rigorous consent and getting the Baylor IRB involved. She and I talked at Cold Spring Harbor—if she had any concerns about Watson’s persona or that the sequencing of his genome might be perceived as self-serving, she did not betray them.

  “I think this is a really unique opportunity,” she told me. “He is someone who has extraordinary knowledge and expertise on all of these issues, one of which is: How do we get people to understand the meaning of the data that we’re generating? That is a tremendous challenge, especially when we don’t understand much of it ourselves. If anybody’s going to understand it, it’s him. At the same time we could think about the future when these special circumstances are not going to be present. With him we didn’t have to worry about the vulnerability aspects.”

  She was hopeful that Watson and his ilk would allow the bioethics issues surrounding personal genomics to be dealt with beforehand (again, this was before Watson’s public meltdown). “I don’t like being reactive—it’s not fun when the shit hits the fan. It only takes one example to set us back so far—look at the Jesse Gelsinger case.”*40

  I told her she sounded like George.

  National Human Genome Research Institute director Francis Collins was at the meeting. I braced myself for the party line about traditional modes of informed consent, and genomics as the fountain of youth and proof of God’s egalitarian plan for humanity. (Collins was a born-again evangelical Christian and prone to invoke religious imagery in his pronouncements about the human genome. In 2009, shortly before he was nominated to the directorship of the NIH, he launched the BioLogos Foundation,41 which “promotes the search for truth in both the natural and spiritual realms, and seeks to harmonize these different perspectives.”)42

  At Cold Spring Harbor, Collins moderated an evening panel on the discovery of genes that appeared to have been selected for in humans during the course of evolution.43 It was and is a topic raising all of the usual bugaboos about race and ethnicity in genetic and genomic research (and the very topic that would get Watson in deep doo-doo a few months later). Have some human traits been selected for in specific human populations but not others? And the uncomfortable corollary: Are some ethnic groups stronger, faster, smarter than others? It is a rich, controversial, and fascinating question similar to the most provocative ones raised by the PGP: At the biological level, what are we? And what do our differences mean?

  Despite his casual dress—jeans and blue-striped golf shirt—Collins appeared to be a bit ill at ease. He spoke without identifying specific researchers: “There was a paper published in a very prominent journal suggesting a signature of selection… .”

  The paper he referred to made claims that a particular gene had been favored over the course of evolution by playing a role in brain size and therefore, it implied, intelligence.44 Scientifically it was a real stretch, but Science ate it up, no doubt because it was such a sexy and controversial story. I listened as Collins went on to exult in the fact that subsequent work showed the connection between this particular gene and intelligence not to be real. Others on the panel chimed in on the paper in question and the delicate business of doing this kind of research. Collins seemed relieved when the subject was changed. At one point during the Q&A he said, “I won’t go to IQ because that’s probably the most explosive, but let’s talk about athletic performance.” It seemed to me something of an Orwellian moment: the world’s most visible genome scientist felt the need to censor himself in public. He was, in many ways, the anti-Watson.

  The next day, between talks I was stalking another übergeneticist when I practically bumped into Collins, who towered over me. I introduced myself and made a lame, passive-aggressive joke about not being able to get through his human firewall of an assistant. I told him I was hanging around George Church, documenting what the PGP was doing. (Was I committing some ethical breach by not disclosing my status as a PGP subject? Probably.) I asked if he would say something on the record about personal genomics. He would not.

  I asked him about 454 sequencing Watson, the biotech company Illumina sequencing a Yoruba man, Craig Venter sequencing himself, and George launching the PGP. He was dismissive of all of it. He thought it unfortunate that this was what I was focusing on. He gave me the impression that he thought these high-profile white-guy sequencing efforts were guided by Narcissus. He hoped that this would be a brief, transient chapter in the history of our field. The public, he suggested, would not understand these efforts and would be turned off by them.

  When I told him I couldn’t speak to what the other
s were doing but that I believed George’s goal was to scale up to thousands or even millions of people and to have the first few people sequenced be those who could sustain any unintended consequences as a means to that end, Collins was unpersuaded. He intimated that it was a self-interested, “look at me” approach to genomics. His bottom line seemed to be that this was an elitist approach, a step in the wrong direction.

  The conversation was over.

  In the bar/café I saw a man in a kelly green sweater and porkpie hat buying an iced coffee and a huge Danish. Still reeling from my encounter with Collins, I approached feebly and told him I was writing a book on personal genomics and asked him if he would speak to me. “Sure, but I don’t have much time,” said Watson.

  Like Collins, Watson didn’t want me to record him, though his demurral was somewhat gentler. He mentioned a magazine article in which he was portrayed as anti-Semitic, which he assured me he was not. In fact, he told me that his father admired the Jews because “they don’t believe in God—they use reason.” And so he therefore considered himself to be “culturally Jewish.” Oy.

  We moved to the veranda. Watson leaned against the railing, his face framed by a swaying stand of trees and the harbor in the background. This brought to mind the famous 1953 photograph of Watson and Crick standing with obvious pride in front of their model of DNA. Crick—all sideburns, ears, nose, and especially eyebrows—is standing on the platform upon which the giant helix is fixed, his left hand on his knee, his right gently resting on the sugar-phosphate backbone of the molecule, a small ruler between his fingers. Watson—rumpled shirt, skinny tie, and unruly pompadour—is looking not at the model or Crick or the camera. Rather, his attention is to something somewhere offstage, his smile at once knowing and mischievous. His face appears to be saying, “I can’t believe this! And I’ve only just turned twenty-five!” Standing on the sun-dappled deck with him fifty-four years later, I could have sworn he was wearing the same expression.